期刊
MOLECULAR PHARMACEUTICS
卷 14, 期 10, 页码 3457-3463出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.7b00464
关键词
ovarian cancer; molecular imaging; near-infrared fluorescence imaging; image-guided surgery; folate receptor alpha targeted imaging
Complete resection of tumor lesions in advanced stage ovarian cancer patients is of utmost importance, since the extent of residual disease after surgery strongly affects survival. Intraoperative imaging may be useful to improve surgery in these patients. Farletuzumab is a humanized IgGl antibody that specifically recognizes the folate receptor alpha (FR alpha). Labeled with a radiolabel and a fluorescent dye, farletuzumab may be used for the intraoperative detection of ovarian cancer lesions. The current aim is to demonstrate the feasibility of FR alpha-targeted dual-modality imaging using In-111-farletuzumab-IRDye800CW in an intraperitoneal ovarian cancer model. Biodistribution studies were performed 3 days after injection of 3, 10, 30, or 100 mu g of In-111-farletuzumab-IRDye800CW in mice with subcutaneous IGROV-1 tumors (5 mice per group). In mice with intraperitoneal IGROV-1 tumors the nonspecific uptake of In-111-farletuzumab-IRDye800CW was determined by coinjecting an excess of unlabeled farletuzumab. MicroSPECT/CT and fluorescence imaging were performed 3 days after injection of 10 mu g of In-111-farletuzumab-IRDye800CW. FR alpha expression in tumors was determined immunobistochemically. Optimal tumor-to-blood-ratios (3.4-3.7) were obtained at protein doses up to 30 mu g. Multiple intra-abdominal tumor lesions were clearly visualized by microSPECT/CT, while uptake in normal tissues was limited. Fluorescence imaging was used to visualize and guide resection of superficial tumors. Coinjection of an excess of unlabeled farletuzumab significantly decreased tumor uptake of In-111-farletuzumab-IRDye800CW (69.4 +/- 27.6 versus 18.3 +/- 2.2% ID/g, p < 0.05) Immunohistochemical analyses demonstrated that the radioactive and fluorescent signal corresponded with FR alpha-expressing tumor lesions. FR alpha-targeted SPECT/fluorescence imaging using In-111-farletuzumab-IRDye800CW can be used to detect ovarian cancer in vivo and could be a valuable tool for enhanced intraoperative tumor visualization in patients with intraperitoneal metastases of ovarian cancer.
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